KR840001139A - Method for preparing 3-amino- [1] benzazin-2-one-1-alkanoic acid - Google Patents

Abstract

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Description

Method for preparing 3-amino- [1] benzazin-2-one-1-alkanoic acid

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Claims (17)

a) any primary and secondary amino group present in any one of the substituents X, R _A , R _B , R, R ₃ , R ₄ and R ₅ in the presence of a reducing agent in a compound of formula (II) Optionally temporarily protects the hydroxy and / or oxo group and alkylates with a compound of formula (IIIA) or a compound of formula (IV) to derive R _A , or b) a compound of formula (V) Temporarily protects any primary and secondary amino groups and / or optionally hydroxy and / or oxo groups present in any one of residues X, R _A , R _B , R ₃ , R ₄ and R ₅ , and Alkylated with a compound of formula (IIIB), or c) a compound of formula (VI), provided that if Y is oxo temporarily protect the oxo group present as substituent X in the presence of a reducing agent Or condensed with an amine of d), or d) the cyano group (s) Solvolysis or e) cyclization of a compound of formula (I) or an ester thereof or f) a compound structurally identical to a compound of formula (I), A double bond or an additional double bond between a nitrogen atom and an adjacent carbon atom in group R _A ) is treated with a reducing agent to saturate the double bond, or g) a compound of formula (I) To produce a compound of the general formula (X) condensed with an amine of the general formula (h); and h) if desired, the resulting compound of the general formula (I) is different from the general formula (I) Or i) if desired, converting the resulting compound of formula (I) having salt-forming characteristics into a salt thereof or releasing a free-form compound from such a salt and / or j ) Bar If appropriate, convert the resulting compound of formula (I), which is characterized by complex-forming, into its complex or k) if necessary, the optical isomer of a special electron arrangement having at least one chiral center. 3-amino- [1] benzazin-2-one-1-alkanoic acid, salts, complexes thereof of formula (I), characterized in that they are supplemented from stereoisomeric mixtures of the resulting compounds of formula (I) And methods of preparing stereoisomers. In the above formula R _A and R _B are groups of the formula Wherein each R ₀ is carboxy or functionally modified carboxy; R ₁ is hydrogen, lower alkyl, amino (lower) alkyl, aryl (lower) alkyl, cycloalkyl or cycloalkyl (lower) alkyl; R ₂ is hydrogen Or lower alkyl) R ₃ and R ₄ are each hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, hydroxy, halogen, trifluoromethyl or together lower alkylenedioxy; R ₅ is hydrogen or lower alkyl; X is 1 hydroxy with oxo, 2 hydrogen, or 1 hydrogen, and the carbocyclic ring is hexahydro or 6,7,8,9-tetrahydro; Z is a reactive esterified hydroxyl group; R _A ′ is hydrogen or R _A described above; Y is a reactive esterified hydroxy group Z with oxo or hydrogen; One of R ₀ ′ and R ₀ ″ is cyano and the other is cyano or R ₀ described above. The general formula of claim 1, wherein one or both of R ₀ represented by COR ₆ in group R _A and R ₀ represented by COR ₇ in group R _B are each carboxy, esterified carboxy, carbamoyl or substituted carbamoyl. A process for preparing the compound of (I), a salt thereof, or a complex compound. 3. The compound of claim 2, wherein one or both of R ₆ and R ₇ are hydroxy, lower alkoxy, (amino, mono- or di-lower alkylamino) -substituted lower alkoxy, carboxy-substituted lower alkoxy, lower alkoxycarbo Nim-substituted lower alkoxy, aryl-substituted lower alkoxy (hydroxy, lower alkanoyloxy or lower alkoxy) -substituted lower alkoxy, (hydroxy, lower alkanoyloxy or lower alkoxy) -substituted lower alkoxymethoxy , Bicyclo alkoxycarbonyl-substituted lower alkoxy, 3-phthalidoxy, (lower alkyl, lower alkoxy, halo) -substituted 3-phthalidoxy, amino, lower alkylamino, di-lower alkylamino, di- Lower alkylamino (both alkyl groups are linked to a carbon bond by carbon atoms and form together with the amino nitrogen a 5,6- or 7-membered heterocyclic ring), (amino or acylamino) -substituted lower alkylamino , α- (carboxy or lower alkoxy To prepare a compound of formula (I), a salt or a complex thereof, which is carbonyl) -substituted lower alkylamino, aryl-substituted loweralkylamino (which may be substituted with carboxy or lower alkoxycarbonyl in α-carbon) Way. c) condensation of a compound of formula (II ') with a compound of formula (IV') under reductive alkylation conditions or a compound of formula (II ') Condensation with a compound of, d) optionally hydrolyzing or derivatizing the product, e) converting the resulting compound of formula (IA) to another compound of the invention, or b) conditions of basic catalysis Under condensation of a compound of formula (V ′) with a compound of formula (IIIB), c) optionally hydrolyzing or derivatizing the product, d) optionally seeing the resulting compound of formula (I) Converted to another compound of the invention, or a) a compound of formula (VII ') is condensed with a compound of formula (VI') under reductive N-alkylation conditions or a formula (IIA ') To a compound of the general formula (VI '), wherein X ″ is oxo and Y is hydrogen and one reactively esterified or etherified hydroxy) or a 3,4-dehydrogenation product thereof or with a 3,4-dehydrogen derivative thereof, b ) The product is optionally reduced, hydrolyzed or derivatized, c) the resulting compound is optionally converted to another compound of the invention and / or if necessary, the resultant free-form compound is converted into a salt or a complex, or Conversion to free compounds or other salts, if necessary, the mixture of isomers or racemic compounds obtained is decomposed into single isomers or racemic compounds, and if necessary the racemic compounds are decomposed into optical colons , A process for preparing a compound of formula (IA), a salt thereof, or a complex compound. In the above formula R ₁ is hydrogen, lower alkyl, amino (lower) alkyl, aryl, aryl (lower) alkyl; Cycloalkyl (lower) alkyl; R ₂ and R ₅ are hydrogen or lower alkyl; R ₃ and R ₄ are hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, hydroxy, halogen, trifluoromethyl or together lower alkylenedioxy; X is oxo, two hydrogens or one hydroxy group and one hydrogen; R ₆ and R ₇ are hydroxy, amino, mono- or di- (lower) alkylamino, lower alkoxy, aryl (lower) alkoxy, lower alkanoyloxymethoxy, (amino, mono- or di-loweralkylamino, respectively) , Carboxy or lower alkoxycarbonyl) -lower alkoxy; R ₃ ′ and R ₄ ′ are hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, halogen, trifluoromethyl or together lower alkylene dioxy; X 'is oxo protected in the form of two hydrogens, one hydrogen and one etherified or esterified hydroxy, oxo or ketal or thioketal; R ₂ ′ and R ₅ ′ are hydrogen or lower alkyl; R ₆ ′ is hydroxy, di (lower) alkylamino, lower alkoxy, atyl (lower) alkoxy, lower alkanoyloxymethoxy or lower alkoxycarbonyl (lower) alkoxy; R ₇ ′ is hydroxy, amino, mono- or di (lower) -alkylamino, lower alkoxy, aryl (lower) alkoxy, lower alkanoyloxymethoxy, di (lower alkylamino) lower alkoxy or lower alkoxycarbonyl ( Lower) alkoxy; R ₁ ′ is hydrogen, lower alkyl, acylated amino (lower) alkyl, aryl, aryl (lower) alkyl, cycloalkyl (lower) alkyl; Z is reactively esterified hydroxy; R ₁ "is hydrogen, lower alkyl, acylated amino (lower) alkyl, aryl, aryl (lower) alkyl, cycloalkyl (lower) alkyl; R ₂ " is hydrogen or lower alkyl; R ₃ "'and R ₄ " are hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, halogen, trifluoromethyl or together lower alkylenedioxy; R ₅ ″ is hydrogen or lower alkyl; R ₆ ″ is hydrogen, di (lower) alkylamino, lower alkoxy, aryl (lower) alkoxy, lower alkanoyloxymethoxy or lower alkoxycarbonyl (lower) alkoxy; R ₇ ″ is hydroxy, di (lower) alkylamino, lower alkoxy, aryl (lower) alkoxy, lower alkanoyloxymethoxy or lower alkoxycarbonyl (lower) alkoxy; X ″ is oxo protected in the form of two hydrogens, one hydrogen and one etherified or esterified hydroxy, oxo or ketal or thioketal; Y is oxo or dichloro. 5. The compound of claim 4, wherein R ₁ is hydrogen, lower alkyl, amino (lower) alkyl, aryl (lower) alkyl (aryl is loweralkyl, hydroxy, loweralkoxy, loweralkylenedioxy, lower alkylnoyloxy, halogen or tri Phenyl mono- or di-substituted or unsubstituted with fluoromethyl), R ₂ and R ₅ are hydrogen or lower alkyl, R ₃ and R ₄ are hydrogen, lower alkoxy, lower alkyl, halogen or trifluor Romethyl or alkylene dioxy together, X is oxo, one hydroxy and one hydrogen, or two hydrogen, R ₆ and R ₇ are hydroxy, amino, lower alkoxy, phenyl (lower) alkoxy, respectively. And lower alkoxycarbonyl (lower) alkoxy. A method for producing a compound of formula (IA), a salt or a complex thereof. 5. The compound of claim 4 wherein R ₁ is hydrogen, lower alkyl, ω-amino (lower) alkyl, aryl (lower) alkyl (aryl is loweralkyl, hydroxy, loweralkoxy, lower alkanoyloxy, halogen or trifluoro methyl Mono-substituted or unsubstituted phenyl), R ₂ and R ₅ are hydrogen or lower alkyl, R ₃ and R ₄ are hydrogen, lower alkoxy, lower alkyl, halogen or trifluoro methyl or together lower Alkylenedioxy, X is oxo, 1 hydroxy and 1 hydrogen, or 2 hydrogen, R ₆ and R ₇ are hydroxy, amino, lower alkoxy, phenyl (lower) alkoxy, lower alkoxycarbonyl ( Lower) alkoxy, a process for the preparation of compounds of formula (IA), salts or complexes thereof. The process of claim 4, wherein the compound of formula (IB), a salt thereof, or a complex compound thereof is prepared. In the above formula n is an integer from 1 to 4; R ₈ is phenyl mono-substituted or unsubstituted with hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, halogen, hydroxy or trifluoromethyl; R ₆ and R ₇ are hydroxy, lower alkoxy up to 4 carbon atoms, benzyloxy or amino, respectively. 5. The compound of claim 4 wherein 1-carboxymethyl-3- (1-ethoxycarbonyl-3-phenyl propylamino) -2,3,4,5-tetrahydro-1H- [1] benzazin-2- Silver, a method for producing a salt or stereoisomer thereof. The method of claim 4, wherein the racemic compound, the optical colon or salt thereof, having a solid solution point of the compound named in claim 8. The method of claim 4, wherein the racemic compound, the optical colon or salt thereof, having a low melting point of the compound named in claim 8. 5. The compound of claim 4 wherein 1-carboxymethyl-3S- (1S-ethoxycarbonyl-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H- [1] benzazin-2- Method of preparing a ions or salts thereof. The compound according to claim 4, wherein 1-carboxymethyl-3- (1-carboxy-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H- [1] benzazin-2- is Process for preparing salts or stereoisomers. The compound according to claim 4, wherein 1-carboxymethyl-3S- (1S-carboxy-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H- [1] benzazin-2-silver or its How to prepare a salt. The method of claim 4, wherein 1-ethoxycarbonylmethyl-3- (1-carboxy-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H- [1] benzazin-2- Silver, a method for producing a salt or stereoisomer thereof. The process of claim 4, wherein the racemic isomeric compound B or salt thereof of the compound named in claim 14 is prepared. The compound according to claim 1, wherein 1-carboxymethyl-7-chloro-3- (1-hydroxycarbonyl-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H- [1] benzase A process for preparing racemic isomer compound B or a salt thereof of pin-2-silver. The compound of claim 1, wherein 3- (1-benzyloxycarbonyl-3-phenylpropylamino) -1-carboxymethyl-2,3,4,5-tetrahydro-1H- [1] benzazin-2- Silver, a method for producing a salt or stereoisomer thereof. ※ Note: The disclosure is based on the initial application.